The ultimate goal of this research is to use the knowledge gained from the identification and characterization of Campylobacter jejuni virulence determinants to reduce morbidity and mortality resulting from C. jejuni infections. C. jejuni is a leading cause of human gastrointestinal disease worldwide, causing approximately 3.5 million cases of diarrheal illness per year in the United States. Infection with C. jejuni is characterized by fever, severe abdominal cramps, and diarrhea containing blood and leukocytes. The dysenteric nature of Campylobacter infection, coupled with experimental evidence, supports the notion that C. jejuni must invade the cells lining the gastrointestinal tract for the development of C. jejuni-mediated enteritis. The focus of this proposal is to identify and functionally characterize the bacterial proteins necessary for C. jejuni internalization. Previous work in my laboratory has revealed that C. jejuni synthesize and secrete proteins upon co-cultivation with mammalian cells. These secreted bacterial proteins have been collectively called Campylobacter invasion antigens (Cia). A mutation in a gene encoding the 73 kDa CiaB secreted protein results in a non-invasive phenotype. I hypothesize that Cia proteins are secreted via a Type III export pathway from C. jejuni. The results of this research will better define the pathogenic mechanisms and virulence determinants of one enteric pathogen, C. jejuni, and will be useful in the development of intervention and control methods to reduce the number of cases of human campylobacteriosis.